Endoscopic ultrasound-rendezvous versus percutaneous-endoscopic rendezvous endoscopic retrograde cholangiopancreatography for bile duct access: Systematic review and meta-analysis.

OBJECTIVES: Endoscopic ultrasound (EUS) or percutaneous-assisted antegrade guidewire insertion can be used to achieve biliary access when standard endoscopic retrograde cholangiopancreatography (ERCP) fails. We conducted a systematic review and meta-analysis to evaluate and compare the effectiveness and safety of EUS-assisted rendezvous (EUS-RV) and percutaneous rendezvous (PERC-RV) ERCP. METHODS: We searched multiple databases from inception to September 2022 to identify studies reporting on EUS-RV and PERC-RV in failed ERCP. A random-effects model was used to summarize the pooled rates of technical success and adverse events with 95% confidence interval (CI). RESULTS: In total, 524 patients (19 studies) and 591 patients (12 studies) were managed by EUS-RV and PERC-RV, respectively. The pooled technical successes were 88.7% (95% CI 84.6-92.8%, I2 = 70.5%) for EUS-RV and 94.1% (95% CI 91.1-97.1%, I2 = 59.2%) for PERC-RV (P = 0.088). The technical success rates of EUS-RV and PERC-RV were comparable in subgroups of benign diseases (89.2% vs. 95.8%, P = 0.068), malignant diseases (90.3% vs. 95.5%, P = 0.193), and normal anatomy (90.7% vs. 95.9%, P = 0.240). However, patients with surgically altered anatomy had poorer technical success after EUS-RV than after PERC-RV (58.7% vs. 93.1%, P = 0.036). The pooled rates of overall adverse events were 9.8% for EUS-RV and 13.4% for PERC-RV (P = 0.686). CONCLUSIONS: Both EUS-RV and PERC-RV have exhibited high technical success rates. When standard ERCP fails, EUS-RV and PERC-RV are comparably effective rescue techniques if adequate expertise and facilities are feasible. However, in patients with surgically altered anatomy, PERC-RV might be the preferred choice over EUS-RV because of its higher technical success rate.

Differentiation of autoimmune pancreatitis from pancreatic adenocarcinoma using CT characteristics: a systematic review and meta-analysis.

OBJECTIVES: To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic accuracy. METHODS: A systematic and detailed literature review was performed through PubMed, EMBASE, and the Cochrane library. Similar descriptors to embody the identical image finding were labeled as a single CT characteristic. We calculated the pooled diagnostic odds ratios (DORs) of each CT characteristic using a bivariate random-effects model. RESULTS: A total of 145 various descriptors from 15 studies (including 562 AIP and 869 PDAC patients) were categorized into 16 CT characteristics. According to the pooled DOR, 16 CT characteristics were classified into three groups (suggesting AIP, suggesting PDAC, and not informational). Seven characteristics suggesting AIP were diffuse pancreatic enlargement (DOR, 48), delayed homogeneous enhancement (DOR, 46), capsule-like rim (DOR, 34), multiple pancreatic masses (DOR, 16), renal involvement (DOR, 15), retroperitoneal fibrosis (DOR, 13), and bile duct involvement (DOR, 8). Delayed homogeneous enhancement showed a pooled sensitivity of 83% and specificity of 85%. The other six characteristics showed relatively low sensitivity (12-63%) but high specificity (93-99%). Four characteristics suggesting PDAC were discrete pancreatic mass (DOR, 23), pancreatic duct cutoff (DOR, 16), upstream main pancreatic duct dilatation (DOR, 8), and upstream parenchymal atrophy (DOR, 7). CONCLUSION: Eleven CT characteristics were informational to distinguish AIP from PDAC. Diffuse pancreatic enlargement, delayed homogeneous enhancement, and capsule-like rim suggested AIP with the highest DORs, whereas discrete pancreatic mass suggested PDAC. However, pooled sensitivities of informational CT characteristics were moderate. CLINICAL RELEVANCE STATEMENT: This meta-analysis underscores eleven distinctive CT characteristics that aid in differentiating autoimmune pancreatitis from pancreatic adenocarcinoma, potentially preventing misdiagnoses in patients presenting with focal/diffuse pancreatic enlargement. KEY POINTS: • Diffuse pancreatic enlargement (pooled diagnostic odds ratio [DOR], 48), delayed homogeneous enhancement (46), and capsule-like rim (34) were CT characteristics suggesting autoimmune pancreatitis. • The CT characteristics suggesting autoimmune pancreatitis, except delayed homogeneous enhancement, had a general tendency to show relatively low sensitivity (12-63%) but high specificity (93-99%). • Discrete pancreatic mass (pooled diagnostic odds ratio, 23) was the CT characteristic suggesting pancreatic ductal adenocarcinoma with the highest pooled DORs.

Effectiveness and complication rates of percutaneous transhepatic fluoroscopy-guided management of common bile duct stones: a single-arm meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis to determine the success and complication rate of percutaneous transhepatic fluoroscopy-guided management (PTFM) for the removal of common bile duct stones (CBDS). METHODS: A comprehensive literature search of multiple databases was conducted to identify original articles published between January 2010 and June 2022, reporting the success rate of PTFM for the removal of CBDS. A random-effect model was used to summarize the pooled rates of success and complications with 95% confidence intervals (CIs). RESULTS: Eighteen studies involving 2554 patients met the inclusion criteria and were included in the meta-analysis. Failed or infeasible endoscopic management was the most common indication of PTFM. The meta-analytic summary estimates of PTFM for the removal of CBDS were as follows: rate of overall stone clearance 97.1% (95% CI, 95.7-98.5%); stone clearance at first attempt 80.5% (95% CI, 72.3-88.6%); overall complications 13.8% (95% CI, 9.7-18.0%); major complications 2.8% (95% CI, 1.4-4.2%); and minor complications 9.3% (95% CI, 5.7-12.8%). Egger's tests showed the presence of publication bias with respect to the overall complications (p = 0.049). Transcholecystic management of CBDS had an 88.5% pooled rate for overall stone clearance (95% CI, 81.2-95.7%), with a 23.0% rate for complications (95% CI, 5.7-40.4%). CONCLUSION: The systematic review and meta-analysis answer the questions of the overall stone clearance, clearance at first attempt, and complication rate of PTFM by summarizing the available literature. Percutaneous management could be considered in cases with failed or infeasible endoscopic management of CBDS. CLINICAL RELEVANCE STATEMENT: This meta-analysis highlights the excellent stone clearance rate achieved through percutaneous transhepatic fluoroscopy-guided removal of common bile duct stones, potentially influencing clinical decision-making when endoscopic treatment is not feasible. KEY POINTS: • Percutaneous transhepatic fluoroscopy-guided management of common bile duct stones had a pooled rate of 97.1% for overall stone clearance and 80.5% for clearance at the first attempt. • Percutaneous transhepatic management of common bile duct stones had an overall complication rate of 13.8%, including a major complication rate of 2.8%. • Percutaneous transcholecystic management of common bile duct stones had an overall stone clearance rate of 88.5% and a complication rate of 23.0%.

Long-term outcomes of endoscopic papillectomy for ampullary adenoma with high-grade dysplasia or adenocarcinoma: a propensity score-matched analysis.

BACKGROUND: Evidence of endoscopic papillectomy (EP) for ampullar adenoma with high-grade dysplasia (HGD) or adenocarcinoma is insufficient. Here we investigated the long-term outcomes of the advanced ampullary tumors treated by EP with careful surveillance comparing to subsequent surgery after EP. METHODS: Patients treated with EP for ampullary adenoma with HGD or adenocarcinoma from the multi-center retrospective Korean cohort of ampulla of Vater tumor were categorized into EP alone versus EP with subsequent surgery groups. The overall survival (OS) and recurrence-free survival (RFS) were analyzed for unmatched and matched cohorts using propensity score with nearest neighbor method. RESULTS: During a median 43.3 months of follow-up, 5-year OS was not significantly different between the EP alone and EP surgery groups (91.9% vs. 82.3%, P = 0.443 for unmatched cohort; 89.2% vs. 82.3%, P = 0.861 for matched cohort, respectively). Furthermore, 5-year RFS was not significantly different between the two groups (82.1% vs. 86.7%, P = 0.520 for unmatched cohort; 66.1% vs. 86.7%, P = 0.052 for matched cohort, respectively). However, the patients with positive both (lateral and deep) margins showed significantly poorer survival outcomes than those with negative margins within the EP alone group (P = 0.007). CONCLUSION: EP alone with careful surveillance showed comparable survival outcomes to those of EP with subsequent surgery for ampullar HGD or adenocarcinoma. Resection margin status could be a parameter to determine whether to perform subsequent radical surgery after EP.

Survival outcome of surgical resection compared to non-resection for Bismuth type IV perihilar cholangiocarcinoma.

BACKGROUND/OBJECTIVES: Bismuth type IV perihilar cholangiocarcinoma has been considered an unresectable disease. The aim of the study was to assess whether the surgical resection of type IV perihilar cholangiocarcinoma was associated with better survival rates. METHODS: The data of 117 patients diagnosed with type IV perihilar cholangiocarcinoma at Keimyung University Dongsan Hospital from 2005 to 2020 were retrospectively reviewed. The Bismuth type was assigned based on the patient's radiological imaging findings. The primary outcomes were the surgical results and median overall survival. RESULTS: The demographic characteristics of the 117 patients with type IV perihilar cholangiocarcinoma were comparable between the surgical resection and non-resection groups. Thirty-two (27.4%) patients underwent surgical resections. A left hepatectomy was performed in 16 patients, right hepatectomy in 13 patients, and a central bi-sectionectomy in three patients. The remaining 85 patients received non-surgical treatments. Thirteen (10.9%) received palliative chemotherapy, and 72 (60.5%) patients received conservative treatment including biliary drainage. The patients in the resection group showed significantly longer median overall survival than the patients in the non-resection group (32.4 vs 16.0 months; P = 0.002), even though the positive resection margin rate was high (62.5%). Surgical complications occurred in 15 (46.9%) patients. Complications of Clavien-Dindo classification grade III or higher occurred in 13 (40.6%) patients and grade V in two patients (6.3%). CONCLUSION: Surgical resection for Bismuth type IV perihilar cholangiocarcinoma is technically demanding. The survival of the resection group was significantly better than that of the non-resection group. The resection of selected patients achieved a curative goal with acceptable postoperative morbidity, although the microscopically positive resection margin rate was high.

Risk of Subsequent Events in Patients With Minor Ischemic Stroke or High-Risk Transient Ischemic Attack.

This study aimed to present the prognosis after minor acute ischemic stroke (AIS) or transient ischemic attack (TIA), using a definition of subsequent stroke in accordance with recent clinical trials. In total, 9,506 patients with minor AIS (National Institutes of Health Stroke Scale ≤ 5) or high-risk TIA (acute lesions or ≥ 50% cerebral artery steno-occlusion) admitted between November 2010 and October 2013 were included. The primary outcome was the composite of stroke (progression of initial event or a subsequent event) and all-cause mortality. The cumulative incidence of stroke or death was 11.2% at 1 month, 13.3% at 3 months and 16.7% at 1 year. Incidence rate of stroke or death in the first month was 12.5 per 100 person-months: highest in patients with large artery atherosclerosis (17.0). The risk of subsequent events shortly after a minor AIS or high-risk TIA was substantial, particularly in patients with large artery atherosclerosis.

Tailored adjuvant gemcitabine versus 5-fluorouracil/folinic acid based on hENT1 immunohistochemical staining in resected pancreatic ductal adenocarcinoma: A biomarker stratified prospective trial.

BACKGROUND: The study aimed to evaluate the clinical outcomes of tailored adjuvant chemotherapy according to human equilibrative nucleoside transporter 1 (hENT1) expression in resected pancreatic ductal adenocarcinoma (PDA). METHODS: Patients who underwent pancreatectomy for PDA were enrolled prospectively. According to intra-tumoral hENT1 expression, the high hENT1 (≥50%) group received gemcitabine and the low hENT1 (<50%) group received 5-fluorouracil plus folinic acid (5-FU/FA). The propensity score-matched control consisted of patients who received hENT1-independent adjuvant chemotherapy. The primary outcome was recurrence free survival (RFS) and the secondary outcomes were overall survival (OS) and toxicities. RESULTS: Between May 2015 and June 2017, we enrolled 44 patients with resected PDA. During a median follow-up period of 28.5 months, the intention-to-treat population showed much longer median RFS [22.9 (95% CI, 11.3-34.5) vs. 10.9 (95% CI, 6.9-14.9) months, P = 0.043] and median OS [36.2 (95% CI, 26.5-45.9) vs. 22.1 (95% CI, 17.7-26.6) months, P = 0.001] compared to the controls. Among 5 patients in the low hENT1 group who discontinued treatment, 2 patients receiving 5-FU/FA discontinued treatment due to drug toxicities (febrile neutropenia and toxic epidermal necrolysis). CONCLUSION: Tailored adjuvant chemotherapy based on hENT1 staining provides excellent clinical outcomes among patients with resected PDA. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02486497.

Development and validation of a simultaneous analytical method for non-steroidal therapeutic compounds in cosmetics using liquid chromatography-tandem mass spectrometry.

Atopic dermatitis is a typical chronic inflammatory skin disease that affects all age groups and requires basic skin care for treatment. Anti-inflammatory and antiallergy steroids are the most frequently used treatments but they are limited due to their side effects caused by a weakening of the immune system. Many consumers focus on performance as a criterion for selecting cosmetics. However, steroids have been illegally used to improve the performance of cosmetics, and consumers have been adversely affected by the corresponding side effects. In this paper, we propose a simple and rapid method using liquid chromatography-tandem mass spectrometry to simultaneously analyze ten non-permitted atopic therapeutic compounds in cosmetic products: chlorpheniramine maleate, ketotifen fumarate, doxepin hydrochloride, azelastine hydrochloride, bufexamac, clotrimazole, tranilast, fusidic acid, tacrolimus, and pimecrolimus. Additionally, the major characteristic fragment ions for tacrolimus, pimecrolimus, and clotrimazole were identified by time-of-flight mass spectrometry. The specificity, linearity, limit of detection, limit of quantification, recovery, precision, accuracy, and stability of the proposed method were validated. The limit of detection and quantification were in the ranges of 5.05-203.30 pg/mL and 15.15-609.90 pg/mL, respectively. The proposed analysis method could help improve the safety management of cosmetics.

The clinical significance of preoperative C-reactive protein/albumin ratio in patients with resected extrahepatic bile duct cancer.

PURPOSE: The C-reactive protein (CRP)/albumin ratio has been identified as a potential prognostic factor for several malignancies. We, therefore, assessed the prognostic role of the CRP/albumin ratio in resected extrahepatic cholangiocarcinoma (EC). MATERIALS AND METHODS: A total of 235 patients were retrospectively analyzed between March 2005 and December 2017. The correlations among the preoperative CRP/albumin ratio, clinicopathological factors, and clinical outcomes were investigated. RESULTS: There were 143 males (60.8%), and the median age at the diagnosis was 70.1 (range 41.0-85.5) years. Patients were diagnosed with perihilar bile duct cancer (n = 61) and distal bile duct cancer (n = 174). The median recurrence-free survival and overall survival were 32.7 and 38.7 months, respectively. The optimal prognostic cut-off point of the CRP/albumin ratio for the survival was 0.18 (× 103). According to the Kaplan-Meier analysis with a log-rank test, the high CRP/albumin ratio group (≥ 0.18) had a significantly shorter overall survival than the low CRP/albumin ratio group (< 0.18) (29.8 vs. 54.6 months, p = 0.002). A multivariate logistic regression analysis for the overall survival showed that CA19-9 ≥ 37 and a high CRP/albumin ratio were associated with a shorter overall survival. CONCLUSION: A high CRP/albumin ratio appears to be significantly associated with clinically worse outcomes in patients with resected EC.

Tolerability and safety of EUS-injected adenovirus-mediated double-suicide gene therapy with chemotherapy in locally advanced pancreatic cancer: a phase 1 trial.

BACKGROUND AND AIMS: Locally advanced pancreatic cancer (LAPC) is challenging. Here, we aimed to evaluate the tolerability and safety of Ad5-yCD/mutTK(SR39)rep-ADP (Ad5-DS), a replication-competent adenovirus-mediated double-suicide gene therapy in combination with gemcitabine in patients with LAPC. METHODS: Patients with newly diagnosed LAPC were enrolled in this single-center, open-label, 3 + 3 dose-escalation phase 1 trial. Ad5-DS was injected into the pancreatic mass with EUS-guided fine needles combined with oral 5-fluorocytosine and valganciclovir, and a standard dose of intravenous gemcitabine. The doses of Ad5-DS in cohorts 1 to 3 were 1 × 1011, 3 × 1011, and 1 × 1012 viral particles (vp)/mL, respectively. Patients were observed for dose-limiting toxicity (DLT) for 8 weeks after Ad5-DS injection. Toxicity within 12 weeks, tumor response in 12 weeks, disease progression in 6.5 months, and detection of adenoviral DNA particles in 8 weeks were also assessed. RESULTS: Among the 11 enrolled patients, 9 completed the evaluation period and 2 withdrew their consent. No DLT was reported; thus, the maximum tolerated dose was not reached. No additional toxicity was reported in 9 to 12 weeks. One patient showed a partial response and 8 showed stable disease at 12 weeks. Two patients showed disease progression at 6.5 months (median progression-free survival, 11.4 months). At 8 weeks, serum adenoviral DNA particles were detected in 4 patients (median, 55 days). CONCLUSION: A combination of intratumoral Ad5-DS and gemcitabine is safe and well tolerated in patients with LAPC. This warrants further investigation in a larger clinical trial. (Clinical trial registration number: NCT02894944.).

Operation time as a simple indicator to predict the overcoming of the learning curve in gastric cancer surgery: a multicenter cohort study.

BACKGROUND: The aim of this study is to identify an indicator to predict the overcoming of the learning curve of distal gastrectomy in gastric cancer surgery. METHOD: A retrospective multicenter cohort study was conducted in 2100 patients who underwent radical distal gastrectomy performed by nine surgeons in eight hospitals between 2001 and 2006. For each surgeon, an individual CUSUM chart was formulated in terms of operation time or clinical outcomes, including severe complications, number of retrieved lymph nodes, positive resection margin, and hospital stay. The actual changing points (CPs) of the CUSUM charts were analyzed. Based on the CP, patients were divided into pre-CP and post-CP groups, and the clinicopathologic outcomes and survival data were compared between the groups. RESULTS: CP determined by operation time was more reliable than CP determined by a combination of clinical outcomes, as the former was correlated not only with short-term outcomes but also with survival. The outcomes were superior in the post-CP group in terms of numbers of harvested lymph nodes, sufficient lymph node harvesting (> 15), and negative proximal margins. In a survival analysis, the post-CP group showed better survival than the pre-CP group in stage II (76% vs 86.1% p = 0.010) and stage III (51.5% vs 60.6% p = 0.042). CONCLUSION: Overcoming the learning curve of distal gastrectomy for gastric cancer can be better predicted by operation time rather than by a combination of postoperative clinical parameters. It is recommended that surgeons initially operate on early stage cancer patients before overcoming the learning curve.

Prospective randomized clinical trial of uncomplicated right-sided colonic diverticulitis: antibiotics versus no antibiotics.

PURPOSE: Antibiotics are widely used in the treatment of uncomplicated left-sided colonic diverticulitis. In Asian countries, however, right-sided colonic diverticulitis is more common than left-sided colonic diverticulitis. The aim of the present study was to evaluate the need for antibiotics in the treatment of uncomplicated right-sided colonic diverticulitis in an Asian population. METHODS: Patients were randomized to two management strategies: antibiotics and no antibiotics. At 4-6 weeks after discharge, the patients in both groups underwent computed tomography or were contacted by phone to confirm the effectiveness of the treatment. The primary end point was the treatment failure rate of the initial treatment, and secondary end points were the length of hospital stay and total admission costs. RESULTS: Patients were randomized to treatment with (61 patients) or without (64 patients) antibiotics. The rates of treatment failure in the antibiotics and no antibiotics groups were 1.7% and 4.6%, respectively, with no significant difference (P = 0.619). There was also no significant difference in the length of hospital stay between the groups (P = 0.983). Total admission costs were lower in the no antibiotics group than in the antibiotics group (US$1004.70 vs US$1112.40, respectively, P = 0.037). CONCLUSION: Conservative management of uncomplicated right-sided colonic diverticulitis without antibiotics shows similar treatment failure rates and length of hospital stay, and is associated with lower hospital costs, compared with standard antibiotic treatment. Therefore, conservative management can be considered as a safe treatment option. TRIAL REGISTRATION: ClinicalTrial.gov No. NCT02314013.

Secondary Breast, Ovarian, and Uterine Cancers After Colorectal Cancer: A Nationwide Population-Based Cohort Study in Korea.

BACKGROUND: The risk of a second primary cancer has increased along with the increasing life expectancies of colorectal cancer survivors. OBJECTIVE: We aimed to evaluate the incidence rate and risk factors of breast and gynecological (ovarian, uterine cervix/corpus) cancers among female colorectal cancer survivors. DESIGN: This is a retrospective population-based cohort study. SETTINGS: This study used data from the National Health Insurance Corporation of Korea. PATIENTS: Each patient with colorectal cancer diagnosed from 2007 to 2012 was followed until 2015 and compared with age-matched women without colorectal cancer at a 1:5 ratio. MAIN OUTCOME MEASURES: The primary outcome was de novo breast/gynecological cancer. Patients with available medical checkup data were included in an additional analysis. RESULTS: We analyzed 56,682 patients with colorectal cancer and 288,119 age-matched noncolorectal cancer controls. The risk of breast/gynecological cancer was higher among patients with colorectal cancer than among controls (HR, 2.91; p < 0.001). The association with colorectal cancer was the highest for ovarian cancer (HR, 6.72), followed by uterine corpus cancer (HR, 3.99), cervical cancer (HR, 2.82), and breast cancer (HR, 1.85). This association remained consistent in the subgroup analysis of medical checkup data (14,190 patients with colorectal cancer, 71,933 controls). Among patients with colorectal cancer, those aged <55 years had a higher risk of breast/gynecological cancers than those aged >55 years (HR, 3.51 vs 2.59), and those with dyslipidemia had a higher risk of breast cancer than those without dyslipidemia (HR, 2.66 vs 2.06). LIMITATIONS: This was a retrospective, population-based study. A prospectively designed study is needed to validate our conclusions. CONCLUSIONS: Compared with the general population, patients with colorectal cancer carry a higher risk of developing secondary breast, ovarian, and uterine cancers. See Video Abstract at http://links.lww.com/DCR/A731.

Effects of Timing of Appendectomy on the Risks of Perforation and Postoperative Complications of Acute Appendicitis.

BACKGROUND: It is generally believed that appendectomy should be performed immediately to prevent perforation and complications. Therefore, our objectives were to investigate the effect of timing of appendectomy on the incidence of perforation and complications. METHODS: We retrospectively reviewed the medical records of patients who underwent laparoscopic appendectomy between January 2014 and June 2015. The time from symptom onset to appendectomy was categorized into three periods: time from symptom onset to hospital admission (symptomatic time), time from admission to appendectomy (hospitalization time), and time from symptom onset to appendectomy [symptomatic period + hospitalization period (overall time)]. Multivariable analyses were performed to identify independent factors associated with perforation and complications. RESULTS: A total of 1753 patients were included in the present study. Perforation occurred in 28.2% of patients, and postoperative complications occurred in 10.0% of patients. Multivariable analysis showed that BT > 38 °C (P = 0.006), WBC count >13,000 cells/µl (P = 0.02), neutrophil ratio >80% (P < 0.001), and symptomatic time >24 h (P < 0.001) were independent factors of appendiceal perforation, while the neutrophil ratio >80% (P < 0.001) and symptomatic time >48 h (P = 0.003) were independently associated with complications. CONCLUSIONS: The present study showed that the symptomatic time and overall time were significantly associated with perforation and complications, whereas hospitalization time was not associated with either perforation or complications.

Prevalence of Malnutrition in Hospitalized Patients: a Multicenter Cross-sectional Study.

BACKGROUND: Malnutrition is associated with many adverse clinical outcomes. The present study aimed to identify the prevalence of malnutrition in hospitalized patients in Korea, evaluate the association between malnutrition and clinical outcomes, and ascertain the risk factors of malnutrition. METHODS: A multicenter cross-sectional study was performed with 300 patients recruited from among the patients admitted in 25 hospitals on January 6, 2014. Nutritional status was assessed by using the Subjective Global Assessment (SGA). Demographic characteristics and underlying diseases were compared according to nutritional status. Logistic regression analysis was performed to identify the risk factors of malnutrition. Clinical outcomes such as rate of admission in intensive care units, length of hospital stay, and survival rate were evaluated. RESULTS: The prevalence of malnutrition in the hospitalized patients was 22.0%. Old age (≥ 70 years), admission for medical treatment or diagnostic work-up, and underlying pulmonary or oncological disease were associated with malnutrition. Old age and admission for medical treatment or diagnostic work-up were identified to be risk factors of malnutrition in the multivariate analysis. Patients with malnutrition had longer hospital stay (SGA A = 7.63 ± 6.03 days, B = 9.02 ± 9.96 days, and C = 12.18 ± 7.24 days, P = 0.018) and lower 90-day survival rate (SGA A = 97.9%, B = 90.7%, and C = 58.3%, P < 0.001). CONCLUSION: Malnutrition was common in hospitalized patients, and resulted in longer hospitalization and associated lower survival rate. The rate of malnutrition tended to be higher when the patient was older than 70 years old or hospitalized for medical treatment or diagnostic work-up compared to elective surgery.

Mechanistic Analysis of Physicochemical Cues in Promoting Human Pluripotent Stem Cell Self-Renewal and Metabolism.

We have previously reported that a porous membrane of polyethylene terephthalate (PET) enables significant augmentation of human pluripotent stem cell (hPSC) proliferation and differentiation. The interaction between hPSCs and the PET surface induces ß-catenin-mediated wingless/integrated (Wnt) signaling, leading to upregulation of the expression of adhesion molecules in hPSCs. In this study, we sought to unveil mechanisms underlying the role of the PET membrane in hPSC self-renewal and metabolism. We discovered that physicochemical cues of the PET membrane considerably alter hPSC metabolism by increasing the cell yield and suppressing the generation of toxic byproduct, indicating an effective cell self-renewal and a less apoptotic culture environment in the membrane culture system. Furthermore, we discovered that a caspase-8 medicated apoptotic pathway plays a profound role in obstructing hPSCs grown on a traditional tissue culture plate (TCP). Treating hPSCs seeded on a TCP surface with a caspase-8 inhibitor significantly suppressed cellular apoptotic pathway and improved cell proliferation and metabolism. Our experimental results provided valuable insights into signal pathways influencing hPSC self-renewal during routine maintenance and expansion, which would shed light on large-scale preparation of hPSCs for clinical applications.

Remote Perturbations in Tertiary Contacts Trigger Ligation of Lysine to the Heme Iron in Cytochrome c.

Perturbations in protein structure define the mechanism of allosteric regulation and biological information transfer. In cytochrome c (cyt c), ligation of Met80 to the heme iron is critical for the protein's electron-transfer (ET) function in oxidative phosphorylation and for suppressing its peroxidase activity in apoptosis. The hard base Lys is a better match for the hard ferric iron than the soft base Met is, suggesting the key role of the protein scaffold in favoring Met ligation. To probe the role of the protein structure in the maintenance of Met ligation, mutations T49V and Y67R/M80A were designed to disrupt hydrogen bonding and packing of the heme coordination loop, respectively. Electronic absorption, nuclear magnetic resonance, and electron paramagnetic resonance spectra reveal that ferric forms of both variants are Lys-ligated at neutral pH. A minor change in the tertiary contacts in T49V, away from the heme coordination loop, appears to be sufficient to execute a change in ligation, suggesting a cross-talk between the different regions of the protein structure and a possibility of built-in conformational switches in cyt c. Analyses of thermodynamic stability, kinetics of Lys binding and dissociation, and the pH-dependent changes in ligation provide a detailed characterization of the Lys coordination in these variants and relate these properties to the extent of structural perturbations. The findings emphasize the importance of the hydrogen-bonding network in controlling ligation of the native Met80 to the heme iron.

Learning curve for gastric cancer surgery based on actual survival.

BACKGROUND: The aim of this study was to investigate learning curves for surgeons performing D2 lymph node dissection based on actual patient survival. METHODS: A total of 3,284 patients with gastric cancer who underwent curative intent gastric cancer surgery by nine surgeons in eight Korean hospitals between 2001 and 2006 were included. Each surgeon's experience was coded as the number of D1 + ß or more gastrectomies performed before that for each patient, which indicates the surgeon's total number of prior surgical experiences. Surgeon experience was grouped into two sets of categories. The set of categories included four groups of experience: ≤50, 51-100, 101-200, and >200 applicable operations. Multivariate survival time regression models were used to evaluate the association between surgeon experience and overall survival. RESULTS: The learning curve for gastric cancer survival after open gastric cancer surgery was steep and did not reach a plateau until a surgeon completed 100 operations. Overall survival rate was the lowest among patients treated by a surgeon with an experience of 50-100 cases. The overall survival of patients at 5 years when the surgeon had a history of more than 100 experiences was higher in each stage than that when the surgeon had a history of fewer than 100 experiences. CONCLUSION: As a surgeon's experience increases, survival after gastric cancer surgery improves. Special attention needs to be paid to the second period of surgeon experience because survival of patients in this period was the lowest.

Decision-making in the management of colonoscopic perforation: a multicentre retrospective study.

BACKGROUND: The incidence of colonoscopic perforation has increased following the widespread use of colonoscopy for the diagnosis and treatment of colorectal disease. The purpose of our study was to compare the clinical outcomes between surgical and non-surgical treatment of colonoscopic perforation. METHODS: We retrospectively reviewed the medical records of patients with colonoscopic perforation, which was treated between January 2005 and December 2014. Patients were divided into two groups depending on whether they received non-surgical (conservative management or endoscopic clipping) or surgical (primary closure, bowel resection and anastomosis, and/or faecal diversion) initial treatment for the perforation. Conversion was defined as the change from a non-surgical to surgical procedure after treatment failure. RESULTS: One hundred and nine patients were analysed. Surgical treatment was more common following diagnostic than therapeutic colonoscopic procedures (74.5 vs. 53.7 %, P = 0.023). Of 55 patients in the non-surgical group, 11 patients required conversion to surgery. The surgical group comprised 54 patients. The complication rate (P = 0.001), and the length of hospital stay (P < 0.001) were significantly greater in the patients requiring conversion than in the surgical group. Multivariate analysis showed that old age, American Society for Anesthesiologists score ≥ 3, and conversion were independent predictors of poor outcomes (P = 0.048, 0.032, and 0.001, respectively). Only perforation size was associated with conversion in multivariate analysis (P = 0.022). CONCLUSION: It is important to select an appropriate treatment in patients with colonoscopic perforation. To avoid non-surgical treatment failure, surgery should be considered in patients with a large perforation. By decreasing the rate of conversion, we might reduce the complication and mortality rates associated with colonoscopic perforation.